Although the "hydrogen bomb" method was reported as 54% yield by Dubococvich, Boehringer Sohn achieved 96% for this step. The difference is that B.I. conducted their hydrogenation under normal pressure at 50°C for 5 hours, whereas Dubocovich conducted theirs at 100 lbs/in2 hydrogen heated to 35°C. This proves that the hydrogenation step proceeds favorably under milder conditions.
ThePictet–Spengler reaction between tryptamine [61-54-1] (1) and benzaldehyde gives 1-Phenyl-tetrahydrocarboline [3790-45-2] (2). Catalytic hydrogenation leads to 2-Benzyltryptamine [22294-23-1] (3). Acylation with acetic anhydride only gave 21% yield of Luzindole (4).
^Dubocovich ML, Mogilnicka E, Areso PM (July 1990). "Antidepressant-like activity of the melatonin receptor antagonist, luzindole (N-0774), in the mouse behavioral despair test".European Journal of Pharmacology.182 (2):313–25.doi:10.1016/0014-2999(90)90290-M.PMID2168835.
^Margarita L. Dubocovich, et al. WO1989001472A1 ().
^Margarita L. Dubocovich, et al.,U.S. patent 5,283,343 (1994 to Discovery Therapeutics Inc).
^Schroeder Dr Hans-D, et al. DE1445516 (1968 to CH Boehringer Sohn AG and Co KG).
^Tsotinis, Andrew; Afroudakis, Pandelis (2008). "Melatonin Receptor Antagonist Luzindole: A Facile New Synthesis". Letters in Organic Chemistry. 5 (6): 507–509. doi:10.2174/157017808785740561. ISSN 1570-1786.
^Righi, Marika; Topi, Francesca; Bartolucci, Silvia; Bedini, Annalida; Piersanti, Giovanni; Spadoni, Gilberto (2012). "Synthesis of Tryptamine Derivatives via a Direct, One-Pot Reductive Alkylation of Indoles". The Journal of Organic Chemistry. 77 (14): 6351–6357. doi:10.1021/jo3010028.
